Isoforms

ADA1 is found in most body cells, particularly lymphocytes and macrophages, where it is
present not only in the cytosol and nucleus but also as the ecto-
form on the cell membrane attached to dipeptidyl peptidase-4 (aka,
CD26).

ADA2 was first identified in human spleen.[4]
It was subsequently found in other tissues including the macrophage
where it co-exists with ADA1. The two isoforms regulate the ratio
of adenosine to deoxyadenosine potentiating the killing of
parasites.

Clinical
significance

ADA2 is the predominant form present in human blood plasma and is
increased in many diseases, particularly those associated with the
immune system: for example rheumatoid arthritis, psoriasis and sarcoidosis. The plasma
ADA2 isoform is also increased in most cancers. ADA2 is not
ubiquitous but co-exists with ADA1 only in
monocytes-macrophages.

Total plasma ADA can be measured using high performance
liquid chromatography, enzymatic or colorimetric techniques.
Perhaps the simplest system is the measurement of the ammonia released from adenosine
when broken down to inosine. After incubation of plasma with a
buffered solution of adenosine the ammonia is reacted with a
Berthelot reagent to form a blue colour which is proportionate to
the amount of enzyme activity. To measure ADA2, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) is
added prior to incubation so as to inhibit the enzymatic activity
of ADA1[4]. It is the absence of ADA1 that causes SCID.